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(American Journal of Pathology. 2001;158:1685-1694.)
© 2001 American Society for Investigative Pathology

Regular Articles

Expression of a Novel RNA-Splicing Factor, RA301/Tra2ß, in Vascular Lesions and Its Role in Smooth Muscle Cell Proliferation

Yoshitane Tsukamoto^*, Noriyuki Matsuo, Kentaro Ozawa, Osamu Hori, Toshio Higashi^¶, Junya Nishizaki^¶, Norimitsu Tohnai^¶, Izumi Nagata^¶, Kiyoshi Kawano^||, Chikao Yutani^*, Seiichi Hirota, Yukihiko Kitamura, David M. Stern^** and Satoshi Ogawa

From the Departments of Pathology ^*
and Neurosurgery,^¶
National Cardiovascular Center, Suita City, Japan; Licensing Business Development,
R&D Operations, Dainippon Pharmaceutical Co. Ltd., Suita City, Japan; the Department of Neuroanatomy,
Kanazawa University School of Medicine, Kanazawa City, Japan; the Department of Pathology,^||
Osaka Rosai Hospital, Sakai City, Japan; the Department of Pathology,
Osaka University Graduate School of Medicine, Suita City, Japan; and the Department of Physiology and Cellular Biophysics,^**
College of Physicians and Surgeons, Columbia University, New York, New York

RA301/Tra2ß, a sequence-specific RNA-binding protein, was first cloned as a stress molecule in re-oxygenated astrocytes. In human vascular tissues, we have found enhanced RA301/Tra2ß expression in coronary artery with intimal thickening, and atherosclerotic aorta. Balloon injury to the rat carotid artery induced RA301/Tra2ß transcripts followed by expression of the antigen, which was detected in medial and neointimal vascular smooth muscle cells (VSMCs). In cultured VSMCs, hypoxia/re-oxygenation caused induction of RA301/Tra2ß and was accompanied by cell proliferation, both of which were blocked by the addition of either diphenyl iodonium, a NADPH oxidase inhibitor, PD98059, a mitogen-activated protein kinase kinase inhibitor, or antisense oligonucleotide for RA301/Tra2ß. Consistent with a link between RA301/Tra2ß and cell proliferation, platelet-derived growth factor also induced expression of RA301/Tra2ß in cultured VSMCs. These data suggest a possible role for RA301/Tra2ß in the regulation of VSMC proliferation, especially in the setting of hypoxia/re-oxygenation-induced cell stress.

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